BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

Objective:To investigate the effects of SS31 peptide on cognitive function and cortical oxidative stress in Alzheimer's disease (AD) model mice.Methods:Eighteen SPF grade male 8-month-old APP/PS1 mice were randomly divided into model group and SS31 group according to the random number table method, with nine mice in each group. Additionally, nine C57BL/6J mice with matched weight were selected as the control group. The mice in SS31 group were intraperitoneally injected with SS31 peptide (3 mg/kg, 0.3 mg/mL), while the mice in model group and control group were intraperitoneally injected with an equal volume of 0.9% NaCl solution.The response ability and daily living ability of mice were evaluated by nest building test (NBT).The learning, memory and exploration abilities of mice were assessed by new object recognition (NOR) and Morris water maze test (MWM). ELISA was used to detect the levels of β -amyloid protein (Aβ) and reactive oxygen species (ROS) in cerebral cortex of mice, and immunofluorescence (IF) was used to detect the number of Aβ plaques.Flow cytometry was used to detect neuronal apoptosis rate, Nissl staining was used to detect neuronal damage, and transmission electron microscopy was used to observe neuronal and mitochondrial morphology. Statistical analysis was conducted by SPSS 25.0 software. One-way ANOVA or repeated measures ANOVA or Kruskal-Wallis H test were used for multi-group comparison. Results:(1) The cognitive evaluation results showed that there were statistically significant differences in NBT latency, 15 hour nest building score, and NOR recognition index among the 3 groups of mice ( F=5.488, 6.750, 10.379, all P<0.05), as well as the platform crossing frequency( H=6.742, P<0.05).The time and group interaction of MWM escape latency in the 3 groups of mice were not significant( F=0.975, P=0.460), but the main effect of time and group were significant( F=14.011, 4.173, both P<0.05).The percentage of platform quadrant dwell time in the model group ((22.91 ± 5.16)%) was lower than that in the control group ((39.96±4.69)%) ( P<0.05), but there was no statistically significant difference compared to the SS31 group ((25.18±3.04)%) ( P>0.05). (2) The ELISA results showed that there were statistically significant differences in the levels of Aβ40, Aβ42 and ROS in cerebral cortex of the 3 groups of mice ( F=12.634, 43.670, 7.143, all P<0.01).All the above indicators of cerebral cortex in the model group were higher than those in control group and SS31 group (all P<0.05). The IF results also confirmed that the numbers of Aβ40 and Aβ42 plaques in cerebral cortex of the model group were higher than those of the control group and SS31 group (all P<0.05). (3) The results of flow cytometry and Nissl staining showed that there were statistically significant differences in the apoptosis rate and injury rate of cortical neurons among the 3 groups of mice ( F=234.086, 43.800, both P<0.05), and the two indicators of cortical neurons in the model group were higher than those in control group and SS31 group (all P<0.05). The transmission electron microscopy results showed that compared with the control group, the structure and morphology of cortical neurons and mitochondria in the model group were abnormal, while the structure and morphology of the SS31 group were close to normal. Conclusion:SS31 peptide can improve cognitive function in AD model mice by inhibiting oxidative stress and neuronal apoptosis in cerebral cortex.

Objective To explore the potential diagnostic value of protocadherin 17(PCDH17)and transducer of ERBB2,(TOB1)in gastric cancer,as well as their effects on autophagy and apoptosis in gastric cancer cells,providing novel target insights for gastric canc-er diagnosis.Methods Tissue samples were collected from 120gastric cancer patients,including cancerous and adjacent normal tissues.The expression levels of PCDH17 and TOB1 were assessed via immunohistochemistry.Overexpression of PCDH17 and TOB1 in the AGS gastric cancer cell line was analyzed using real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot.The effects of these overexpressions on cell proliferation,autophagy,and apoptosis were evaluated using CCK-8 assays,Western blot a-nalysis,and detection of autophagy and apoptosis-related proteins.Additionally,receiver operating characteristic(ROC)curve analysis was employed to evaluate the sensitivity and specificity of combined PCDH17 and TOB1 in diagnosing gastric cancer.Results The ex-pression levels of PCDH17 and TOB1 were significantly lower in gastric cancer tissues compared to adjacent normal tissues(P＜0.001),and their low expression was significantly correlated with clinical stage and lymph node metastasis(P＜0.001).In vitro experiments dem-onstrated that overexpression of PCDH17 and TOB1 could significantly inhibited the proliferation of gastric cancer cells(P＜0.001),and promoted autophagy and apoptosis through upregulation of autophagy markers LC3 and Beclin-1,along with pro-apoptotic protein BAX,while downregulating anti-apoptotic protein BCL-2.The combined overexpression of PCDH17 and TOB1 resulted in a more pronounced inhibitory effect on cell proliferation and enhanced levels of autophagy and apoptosis compared to individual overexpression(P＜0.001).The area under the curve for the combined diagnostic efficacy of PCDH17 and TOB1 was 0.887,with a sensitivity of 88.39％,and a spe-cificity of 87.24％,the diagnostic effect was superior to that of individual assays.Conclusion The low expression of PCDH17 and TOB1 is closely associated with the occurrence and progression of gastric cancer.Furthermore,the combined detection of these markers exhibits high sensitivity and specificity for gastric cancer diagnosis.The combined overexpression of PCDH17 and TOB1 had a significant synergistic effects on inhibiting proliferation while promoting autophagy and apoptosis of gastric cancer cells.PCDH17 and TOB1 can be used as po-tential diagnostic biomarkers and therapeutic targets for gastric cancer,providing new avenues for the diagnosis and targeted treatment of gastric cancer.

Objective To investigate the effect of circRNA-homeodomain-interacting protein kinase 2(circHIPK2)on angiotensinⅡ(AngⅡ)-induced apoptosis of vascular endothelial cells through the regulation of the miR-7-5p/transcription factor 4(TCF4)axis.Methods Human umbilical vein endothelial cells(HUVECs)were randomly divided into the control,model,negative control cotrans-fection,circHIPK2 knockdown,miR-7-5p overexpression,and circHIPK2 knockdown+miR-7-5p knockdown groups.Except for the control group,all other groups were administered 10 nmol/L Ang Ⅱ to establish a hypertensive injury model.The circHIPK2,miR-7-5p,and TCF4 mRNA expression levels were detected after transfection.Apoptosis,proliferation,mitochondrial membrane potential,reactive oxygen species(ROS),antioxidant enzymes,pro-inflammatory factors,and TCF4 protein expression were assessed.Results Compared with the control group,the expressions of circHIPK2 and TCF4 mRNA,cell apoptosis rate,relative expression of ROS,levels of IL-6,IL-1β,and IL-18,and expressions of Bax and TCF4 protein increased,and cell viability,miR-7-5p mRNA expression,mitochondrial mem-brane potential,activities of superoxide dismutase(SOD)and catalase(CAT),and Bcl-2 protein expression decreased in the model group(P＜0.05).Both circHIPK2 knockdown and miR-7-5p overexpression reversed Ang Ⅱ-induced pathological changes in vascular endothelial cells.miR-7-5p knockdown reduced the effect of circHIPK2 knockdown on pathological cellular changes in the model group.Conclusion circHIPK2 knockdown can weaken TCF4 expression by upregulating miR-7-5p,thereby reducing Ang Ⅱ-induced inflam-mation and oxidative stress in vascular endothelial cells and ultimately inhibiting cell apoptosis.

Objective:To investigate the distribution of pathogens and changes in serum levels of pyruvate kinase isozyme type M2 (PKM2) and Galectin-3 in patients with severe trauma complicated by ventilator-associated pneumonia (VAP).Methods:A total of 139 patients with severe trauma and underwent mechanical ventilation in Zhangjiakou First Hospital from February 2022 to February 2024 were selected as the study subjects. They were divided into the VAP group (57 cases) and non- VAP group (82 cases) based on whether they developed VAP. The distribution of pathogenic bacteria in the VAP group was analyzed. Enzyme-linked immunosorbent assay (ELISA) method was applied to determine the expression levels of serum PKM2 and Galectin-3. Multivariate Logistic regression was applied to analyze the influencing factors of VAP in patients with severe trauma. Receiver operator characteristic (ROC) curve was applied to analyze the diagnostic value of serum PKM2 and Galectin-3 levels for severe trauma complicated by VAP.Results:Seventy-one strains of pathogenic bacteria were isolated from 57 patients in the VAP group, mainly including Gram positive bacteria (36.62%), Gram negative bacteria (59.15%), and fungi (4.23%). Among them, Gram positive bacteria were mainly Staphylococcus epidermidis and Staphylococcus aureus, Gram negative bacteria were mainly Acinetobacter baumannii and Klebsiella pneumoniae, and fungi were mainly tropical Candida and Candida albicans. The proportion of history of diabetes, the proportion of eating through nasogastric tube, the proportion of trauma severity score ≥ 16 and the levels of serum PKM2 and Galectin-3 in the VAP group were higher than those in the non- VAP group: 54.39%(31/57) vs. 32.93%(27/82), 82.46%(47/57) vs. 52.44%(43/82), 66.67%(38/57) vs. 24.39%(20/82), (32.46 ± 7.28) μg/L vs. (24.25 ± 6.17) μg/L, (3.26 ± 0.75) ng/L vs. (2.39 ± 0.61) ng/L, there were statistical differences ( P<0.05). Serum PKM2, Galectin-3, history of diabetes, nasal feeding mode and trauma severity score were the influencing factors of severe trauma patients complicated by VAP ( P<0.05). The area under the curve (AUC) of serum PKM2, Galectin-3, and their combination in predicting severe trauma complicated by VAP was 0.90, and the combination of the two was superior to their respective individual diagnoses ( Zcombination - PKM2 = 2.00, Zcombination - Galectin-3 = 1.99, P = 0.046, 0.047), its sensitivity and specificity were 92.98% and 84.15%, respectively. Conclusions:The distribution of urinary tract pathogens in patients with severe trauma complicated by VAP is mainly Gram negative bacteria, and serum PKM2 and Galectin-3 levels are obviously increased in patients with severe trauma complicated by VAP . The combination of the two has higher diagnostic value for severe trauma complicated by VAP and certain clinical application value.

Objective:To investigate the expressions and prognostic value of lysyl oxidase like protein 2(LOXL2),chemo-kine c-c-motif ligand 18(CCL-18)and chitinase protein 40(YKL-40)in connective tissue disease with pulmonary interstitial lesions.Methods:A total of 308 patients with connective tissue disease who were treated in the First Affiliated Hospital of Hebei North Univer-sity from July 2021 to February 2022 were selected,including 108 patients with pulmonary interstitial disease(pathological group),200 patients without pulmonary interstitial disease(non pathological group),and another 35 healthy volunteers as the control group.Serum levels of LOXL2,CCL-18 and YKL-40 were detected by ELISA;Logistic regression analysis was applied to analyze the factors affecting the prognosis of patients with connective tissue disease and pulmonary interstitial disease;the predictive value of serum LOXL2,CCL-18 and YKL-40 levels on the prognosis of patients with connective tissue disease and pulmonary interstitial disease was analyzed by receiver operating characteristic(ROC)curve analysis.Results:Compared with control group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the non pathological group and the pathological group were obviously increased(P<0.05);the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the le-sion group were higher than those in the non lesion group(P<0.05);compared with the survival group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease in the death group were obviously higher(P<0.05);Logistic regression analysis showed that LOXL2,CCL-18 and YKL-40 were risk factors for the prognosis of patients with connective tissue disease and pulmonary interstitial disease(P<0.05);the area under the ROC curve(AUC)of the combined detection of serum LOXL2,CCL-18 and YKL-40 in predicting the prognosis of patients with connective tissue disease and pulmonary interstitial disease was 0.967,which was better than their respective independent prediction(Zcombined detection-LOXL2=1.735,P=0.041;Zcombined detection-CCL-18=2.481,P=0.007;Zcombined detection-YKL-40=2.008,P=0.022).Conclusion:The serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease are elevated,which has certain value in the prognosis evaluation of patients with connective tissue disease combined with pulmonary interstitial disease.

Objective To investigate the efficacy of cannabidiol(CBD)in improving renal function and protecting the kidney in mice with unilateral ureteral obstruction(UUO).Methods A total of 24 healthy,8-week-old,WTC57BL/6 male mice were divided into the Sham group,UUO group and UUO+CBD group,with 8 rats in each group.The UUO models were established by ligating one side of the ureter and removing the contralateral kidney to ensure unilateral kidney hydronephrosis.In the UUO+CBD group,5 mg/kg CBD was intraperitoneally injected immediately after the operation,once a day for 10 days.The Sham and UUO groups were given the same amount of normal saline.Blood sample was collected through the inner canthus venous plexus of the orbit 24 hours after the last administration.The levels of serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),superoxide dismutase(SOD),and malondialdehyde(MDA)were detected with an automatic biochemistry analyzer.The histopathological sections were prepared,the pathological changes of renal tissues were observed under a light microscope,and the pathological injuries were scored.Mitochondrial quantity and morphological structure changes were observed with a transmission electron microscopy.Results Compared with the Sham group,the UUO group exhibited significantly higher levels of Scr[(22.55±3.29)μmol/L vs.(12.11±3.32)μmol/L],BUN[(18.62±2.15)mmol/L vs.(10.05±1.19)mmol/L],TNF-α[(21.04±2.56)pg/mL vs.(9.26±0.47)pg/mL],IL-1β[(10.25±1.25)pg/mL vs.(5.44±0.99)pg/mL],and MDA[(31.26±1.17)nmol/mL vs.(17.12±1.39)nmol/mL],but significantly lower level of SOD[(90.26±2.11)U/mL vs.(136.54±3.05)U/mL],all P＜0.000 1.Compared with the UUO group,the UUO+CBD group showed a significant decrease in the levels of Scr[(16.82±0.89)μmol/L vs.(22.55±3.29)μmol/L],BUN[(14.35±0.99)mmol/L vs.(18.62±2.15)mmol/L],TNF-α[(16.29±0.88)pg/mL vs.(21.04±2.56)pg/mL],IL-1β[(6.23±0.95)pg/mL vs.(10.25±1.25)pg/mL],MDA[(20.36±1.23)nmol/mL vs.(31.26±1.17)nmol/mL],and renal pathological damage score[(1.88±0.64)vs.(2.50±0.76)],but a significant increase in SOD level[(117.84±1.57)U/mL vs.(90.26±2.11)U/mL],all P＜0.000 1.Under electron microscopy,mitochondrial swelling,loss of inner membrane structure,and membrane rupture were observed in the UUO group,while the UUO+CBD group showed milder morphological changes.Conclusion CBD improves renal function in UUO model mice through anti-inflammatory,antioxidant and mitochondrial protection,and is a potential therapeutic drug for renal protection in clinic.

Following hemorrhagic shock,locally released chemotactic molecules attract neutrophils to rapidly migrate to the damaged tissues,while effectively bind,engulf and kill microorganisms,along with chromatin releasing and forming a substance deco-rated with a meshwork of microbicidal proteins and enzymes,a DNA-protein structure named neutrophil extracellular traps(NETs).The formation and degradation of NETs are regulated by multiple factors,and an imbalance in the formation and degradation of NETs plays a role in cellular damage and the aggregation of inflammatory factors,which is one of the main mechanisms of uncontrolled in-flammatory response and further aggravates organ damage.Studies have shown that NETs are involved in the process of hemorrhagic shock-induced organ damage,but the relevant mechanisms have not been fully elucidated.In this paper,we review the role of NETs in organ damage after hemorrhagic shock and the related mechanisms,and in order to understand the role of NETs and provide a refer-ence for new targets for the prevention and treatment of hemorrhagic shock.

Objective:To investigate the effect of immune cells in blood and PD-L1 expression in tissues on prognosis of patients with post-surgery of advanced adenocarcinoma of esophagogastric junction(AEGJ)and hyperthermic intraperitoneal chemotherapy(HIPEC)treatment,and to explore the relationship between immune cells and PD-L1 level in patients with post-surgery and HIPEC treatments.Methods:A total of 46 patients with advanced AEGJ surgery and adjuvant HIPEC in the First Affiliated Hospital of Hebei North University from January 2018 to June 2019 were enrolled.Transcriptome sequencing technology was used to examine levels of blood immune cells in patients with AEGJ postoperative adjuvant HIPEC.Immunohistochemistry was applied to detect expression of PD-L1 in tissues of AEGJ,and corresponding statistical methods were used to observe the prediction of immune cells and PD-L1 levels on prognosis of patients with AEGJ,and correlation with each other.Results:As of June 30,2022,the cancer-specific survival rate(CSS),relapse free survival rate(RFS),median CSS and median RFS were 28.26％,45.65％,31 months and 24 months,respective-ly.Positive expression of PD-L1 was 52.17％,ratios of RFS and CSS between positive and negative level of PD-L1 were 16.67％,77.27％and 54.17％,90.91％,respectively;the median time of RFS(12 months vs 37 months)and CSS(24 months vs 37 months)in PD-L1 positive expression was less than those in PD-L1 negative expression separately.A total of 22 kinds of immune cells were exam-ined in this study,compared with CPS<1 group,levels of CD8+T cells,dendritic cells activated and resting NK cells were significantly decreased in CPS≥1 group(all P<0.05),while M2 macrophages in the former group were lower than those in the latter group(0.013±0.012 vs 0.033±0.003,P<0.001).Results of ROC curve showed that CD8+T cells and M2 macrophages were predictor of patients with AEGJ treatments prognosis(AUC=0.690 and 0.698,respectively).COX multivariate regression analysis revealed that CD8+T cell was an independent protective factor for CSS of AEGJ and HIPEC[HR=0.590,95％CI(0.248～0.7080],while M2 macrophage was the risk factors for AEGJ and HIPEC[HR=6.448,95％CI(1.440～9.165)].Positive expression of PD-L1 was positively correlated with level of M2 macrophages(R=0.44,P<0.01),while negatively associated with level of CD8+T cells(R=-0.47,P<0.05).Conclusion:Adjuvant HIPEC therapy maybe regulate the function of M2 macrophage and CD8+T cells,among which the level of M2 macrophage is positively related to PD-L1 expression.The increasing of M2 macrophage cells may be the risk factor for the prognosis of AEGJ patients with surgery and HIPEC-treatment.

Objective To investigate the expression levels and clinical significance of B7 homolog 3(B7-H3),peroxiredoxin 1(PRDX1),and thioredoxin(TRX)in the serum and tissues of patients with ulcerative colitis(UC)and UC-associated colorectal cancer(UC-CRC).Methods A total of 108 patients with UC who underwent examination in our hospital between January 2019 and December 2023 were enrolled in the UC group.Additionally,108 patients with UC-CRC who were examined in our hospital were included in the UC-CRC group.Furthermore,108 individuals without any abnormalities detected during colonoscopy were recruited as the control group.The serum levels of B7-H3,PRDX1,and TRX were quantified using enzyme-linked immunosorbent assay(ELISA).The expression of B7-H3,PRDX1,and TRX in tissues from UC-CRC and UC patients was assessed by immunohis-tochemistry.The diagnostic performance of serum B7-H3,PRDX1,and TRX levels for UC-CRC was evaluated by constructing receiver operating characteristic(ROC)curves.Results Compared with the control group,the serum expression levels of B7-H3,PRDX1,and TRX in both the UC group and the UC-CRC group were significantly elevated in sequence(P<0.05).In comparison to the resting UC group,the serum expression levels of B7-H3,PRDX1,and TRX in the episodic UC group also increased significantly(P<0.05).Furthermore,compared with UC patients,the positive expression rates of B7-H3,PRDX1,and TRX in the tissues of UC-CRC patients were markedly higher(P<0.05).The combination of serum B7-H3,PRDX1,and TRX demonstrated the highest AUC for diagnosing UC-CRC patients,outperforming the individual diagnostic performance of each biomarker(Z combination-B7-H3=2.829,P=0.005,Z combination-PRDX1=2.544,P=0.011,Z combination-TRX=3.673,P<0.001).Conclusion B7-H3,PRDX1,and TRX are significantly overexpressed in both the serum and tissues of UC-CRC patients,and their combined evaluation holds potential as a diagnostic tool for detecting the development of UC-CRC.